Gene Mutations (HL IB Biology)

• A gene mutation is a change in the sequence of base pairs in a DNA molecule; this may result in a new allele
  • Mutations occur all the time and at random
  • There are certain points in the cell cycle when mutations are more likely to occur, for example, copying errors when DNA is being replicated (S phase of interphase)
• As the DNA base sequence determines the sequence of amino acids that make up a polypeptide, mutations in a gene can sometimes lead to a change in the polypeptide that the gene codes for
• Most mutations are harmful or neutral (have no effect) but some can be beneficial
• Inheritance of mutations:
  • Mutations present in normal body cells are not inherited, they are eliminated from the population once those cells die
  • Mutations within gametes are inherited by offspring, possibly causing genetic disease

Substitution mutations

• A mutation that occurs when a nucleotide base in the DNA sequence is randomly swapped for a different base is known as a substitution mutation
• A substitution mutation will only change the amino acid for the triplet (group of three consecutive bases) where the mutation occurs; it will not have a knock-on effect further along the gene/polypeptide

Substitution mutation diagram

Insertion mutations

• A mutation that occurs when a nucleotide (with a new base) is randomly inserted into the DNA sequence is known as an insertion mutation
• An insertion mutation changes the amino acid that would have been coded for by the original base triplet, as it creates a new, different triplet of bases
  • Remember – every group of three bases in a DNA sequence codes for an amino acid
• An insertion mutation also has a knock-on effect by changing the triplets (groups of three bases) further on in the DNA sequence
• This is sometimes known as a frameshift mutation
• This may dramatically change the amino acid sequence produced from this gene and therefore the ability of the polypeptide to function

Insertion mutation diagram

An example of an insertion mutation

Deletion mutations

• A mutation that occurs when a nucleotide (and therefore its base) is randomly deleted from the DNA sequence
• Like an insertion mutation, a deletion mutation changes the amino acid that would have been coded for
• Like an insertion mutation, a deletion mutation also has a knock-on effect by changing the groups of three bases further on in the DNA sequence
• Like an insertion mutation, this is sometimes known as a frameshift mutation
• This may dramatically change the amino acid sequence produced from this gene and therefore the ability of the polypeptide to function

• Mutagenic agents are environmental factors that increase the mutation rate of cells
  
  • Radiation can cause chemical changes in DNA, this includes:
    • High-energy radiation such as UV light
    • Ionising radiation such as X-rays, gamma rays and alpha particles
  • Chemical substances can also caused changes to DNA, examples include
    • Benzo[a]pyrene and nitrosamines found in tobacco smoke
    • Mustard gas used as a chemical weapon in World War I
  • Mutagens can also come from inside the cell such as particular enzymes that either break down DNA or produce substrates that are mutagenic 
• Some mutations may be produced at random, this can happen most frequently during DNA replication and repair where errors in the nucleotide sequence are not detected by the proofreading process carried out by DNA polymerase
  • If the polymerase detects that a wrong nucleotide has been added, it will remove and replace the nucleotide before continuing with DNA synthesis
• Most mutations do not alter the polypeptide or only alter it slightly so that its structure or function is not changed
• As the genetic code is degenerate (more than one triplet code codes for the same amino acid) some mutations will not cause a change in the amino acid sequence

• Mutations can occur anywhere in the base sequence of a genome on all chromosomes in all organisms
  • This is how new strains of viruses or bacteria can come into existence
• Some locations of the genome are more likely to mutate than others
  • Uncoiled DNA has a higher probability of encountering mutations than DNA tightly coiled around a histone as it is more exposed
  • Many mutations occur in non-coding regions of DNA such as satellite DNA
  • Mutation hotspots are regions where mutations are more frequent. One hotspot is where the nucleotide cytosine (C) is followed by guanine (G) and is called a CpG site
    • When methylation occurs here, C can mutate into Thymine (T) in a substitution mutation
    • Where this occurs repeatedly it is known as a CpG island and is associated with particular cancers such as colorectal cancer

Intentional changes to base sequences

• No known mechanisms exist where cells are able to intentionally mutate or change their DNA base sequence
• Proofreading processes exist to change a mutation back into its original sequence but no mechanism exists for making a deliberate change to a base or sequence of bases with the purpose of changing a trait of the organism